We propose to conduct a randomized, double-blind, placebo-controlled, 2x2x2 factorial trial of vitamin C, vitamin E, and beta-carotene in the secondary prevention of cardiovascular disease among women, 40 years of age and older, at high risk for subsequent cardiovascular events due to a prior history of myocardial infarction (MI), stroke, angina pectoris (AP), coronary artery bypass graft (CABG), percutaneous transluminal coronary angioplasty (PTCA), transient cerebral ischemia (TIA), carotid endarterectomy (CEA), or peripheral artery surgery (PAS). The rationale for this trial relates to the known antioxidant properties of these three micronutrients which are postulated to prevent lipoprotein oxidization and thereby prevent or retard atherogenesis. This trial will be conducted among approximately 8000 U.S. female nurses, who will be recruited from a mailing to approximately 1.39 million nurses that will be carried out as part of a companion study of low-dose aspirin (HL 43851) and vitamin E and beta carotene (CA 47988). An invitational letter will be sent to all nurses identified from the larger mailing as potentially eligible. This mailing will include a letter describing the trial, an informed consent form, and a questionnaire soliciting information on past medical history, cardiovascular risk factors, diet, medication and nutritional supplement use, and possible contraindications to use of vitamin C, vitamin E, or beta-carotene. Willing and eligible nurses will be enrolled in a three-month run-in period, during which all participants will receive placebos. At the end of the run-in period, those who are still willing and eligible, and who report having taken their pills at least two-thirds of the time, will be assigned at random to one of eight treatment groups: 1000 mg vitamin C daily in two divided doses or its placebo, 400 mg vitamin E daily in two divided doses or its placebo, and/or 20 mg beta-carotene daily in two divided doses or its placebo. At six-month intervals we will mail a new supply of study capsules and a follow-up questionnaire to each participant asking about compliance, possible side effects, medications, and the incidence of endpoints. Endpoints will be confirmed by review of medical records. Based on our successful experience with the ongoing Physicians' Health Study, the results of a pilot study conducted in nurses, and long-term experience following a large cohort of US nurses, we believe we can provide either definitive positive or informative null results regarding the study hypotheses.